Aerosols represent an important delivery form for the administration of pharmaceutically active agents to patients. Typically, aerosols are homogenous colloidal mixtures that comprise a dispersed phase and a continuous, gaseous medium.
One example of an aerosol is a liquid aerosol in which the dispersed phase is a liquid and the continuous medium is a gas. Liquid aerosols are an important delivery form for the administration of pharmaceutically active agents to patients. Liquid aerosols can be used to deliver diverse categories of pharmaceutically active agents. These pharmaceutically active agents can include small molecules such as cancer treating chemotherapeutic agents, peptide chains such as therapeutic antibodies or vaccine antigens and nucleic acids, such as DNA or siRNA, for gene therapy.
Epithelial tissue lining the lungs, as well as other organs and body cavities, is a very important target tissue for the delivery of pharmaceutical compositions to patients. In fact, the delivery of aerosols to different parts of the respiratory tract, such as the airways and alveoli, may be used to treat a variety of different conditions. These conditions include lung cancer, asthma, bronchitis, bronchiectasis, pneumonia, infectious diseases, tuberculosis, influenza, inflammatory disease, chronic obstructive pulmonary disease, cystic fibrosis, respiratory distress syndrome, Parkinson's disease, diabetes, osteoporosis and systemic diseases such as cardiopulmonary hypertension. The targeted delivery of aerosols containing pharmaceutically active agents also helps avoid side effects associated with the oral, or parenteral, administration of some pharmaceutically active agents.
A significant limitation in the use of aerosols in treating patients has been that only small volumes of aerosols can be delivered to target tissues, such as the lungs, using existing technologies. Aerosols generated by jet, thermal, or ultrasonic methods and delivered by inhalation are relatively slow, highly inefficient and imprecise. They depend upon the ability of the patient to respire a clinically effective dose, that is being directed at the patient's nose and mouth at high speed in relatively low concentrations. If the patient is a newborn with impaired respiratory function, is unconscious or is too physically impaired by disease, the ability to achieve a sufficient concentration in the lungs may not be feasible by inhalation alone. This can have additional consequences. For example, if antibiotics are administered as inhaled therapies via a nebulizer in insufficient concentrations to fully overcome the disease, this may expose the patient to greater likelihood of antibiotic resistance. Aerosol generating methods that depend on compressed air or propellants to generate particles in the 1-5 micron size range which are small enough to be respirable by the patient from outside the body are typically moving at high momentum which can force as much as 95% of the dose against the back of the throat, where it may be coughed up or swallowed. Current inhalation therapies do not permit targeted local/regional drug administration to a lobe or lesion within the lung. They do not protect the nose, mouth, throat, trachea or other sensitive tissues in the respiratory tract from exposure to drugs that may be hazardous or harmful to healthy tissue if respired, such as aerosolized chemotherapy. The small particles size produced by inhalation therapy methods are also more likely to be exhaled by the patient, contaminating the environment and creating potential hazards for caregivers. In addition, these technologies that depend on heat, or propellants, can affect the efficacy and viability of many therapeutic formulations and alter the pharmaceutically and/or biologically active agents that are being delivered. Such inhalation technologies are also incompatible with the administration of drugs in aerosol form to many other target tissues and organs.
Thus, a need exists for apparatuses and methods that may be used to administer efficiently and precisely deliver aerosols to target tissues, and organs, such as the lungs.